inflammatory responses and immune cell populations in skin explants - - PowerPoint PPT Presentation

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inflammatory responses and immune cell populations in skin explants - - PowerPoint PPT Presentation

PUFA-derived bioactive lipids mediate inflammatory responses and immune cell populations in skin explants Alexandra Kendall Nordic LipidForum 6 th June 2015 SLS vs UVR SLS UVR Commonly encountered environmental stressors Exposure to high


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PUFA-derived bioactive lipids mediate inflammatory responses and immune cell populations in skin explants

Alexandra Kendall Nordic LipidForum 6th June 2015

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SLS vs UVR Commonly encountered environmental stressors

  • Exposure to high levels of SLS can causes irritant dermatitis
  • - Dermatology/occupational health problem
  • UVR is an alternative cause of skin erythema
  • Do they affect the same lipid pathways?

UVR SLS

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Ex vivo culture

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Ex vivo treatment

Day 3 (morning): Culture medium replaced Day 2 (morning): Culture medium replaced Day 1 (evening): Delivery and processing of skin SDS-soaked disc applied Day 4 (morning): UVR applied Biopsies taken from centre of pieces of baseline and UV- and SLS-treated skin SDS-soaked disc removed Day 5 (morning):

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Lipoxygenase products

12-lipoxygenase 15-lipoxygenase AA DHA DGLA EPA LA

12-HETE 11-HDHA 14-HDHA 12-HEPE 15-HETE 17-HDHA 15-HETrE 13-HODE

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SLS 12-LOX products

12 HETE 12 HEPE 14 HDHA 11 HDHA 1 10 100 1000 10000 100000

Control 1% SDS 3% SDS 6% SDS

* * * * * * * *

pg/mg protein

15-LOX products

15 HETE 15 HETrE 13 HODE 17 HDHA 1 10 100 1000 10000

Control 1% SDS 3% SDS 6% SDS

* * * * * * * *

pg/mg protein n=4, mean ± SE * p<0.05

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UVR 12-LOX products

12 HETE 12 HEPE 14 HDHA 11 HDHA 1 10 100 1000 10000

Control 4MED 6MED 10MED

pg/mg protein

15-LOX products

15 HETE 15 HETrE 13 HODE 17 HDHA 1 10 100 1000

Control 4MED 6MED 10MED

pg/mg protein n=4, mean ± SE

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N-acyl ethanolamides

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SLS

N-acyl ethanolamides

PEA ALEA LEA OEA STEA EPEA AEA DHEA DGLEA 1 10 100 1000 10000 100000 Control 1% SLS 3% SLS 6% SLS * * * * * pg/mg protein

n=4, mean ± SE * p<0.05

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UVR

N-acyl ethanolamides

PEA ALEA LEA OEA STEA EPEA AEA DHEA DGLEA 1 10 100 1000 10000 Control 4MED 6MED 10MED pg/mg protein

n=4, mean ± SE

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Immune cell population identification

SSC CD45 HLA-DR SSC CD1a CD14 SSC CD3 SSC TCRgd CD56 CD66b SSC CD127 Antigen presenting cells T cells NK cells Granulocytes Innate lymphoid cells

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HLA-DR+ T cells Granulocytes NK cells ILCs HLA-DR+ T cells Granulocytes NK cells ILCs HLA-DR+ T cells Granulocytes NK cells ILCs HLA-DR+ T cells Granulocytes NK cells ILCs

Immune cell populations

  • Inter-individual variation in response
  • Consistent effect was reduction in innate lymphoid cell population
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Despite similar clinical changes in vivo, SLS and UVR elicit different effects in skin explants

Conclusions

SLS UVR 12-LOX products Increase Non-significant increase 15-LOX products Increase No change N-acyl ethanolamides Increase No change Epidermal innate lymphoid cell population Decrease No change

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Acknowledgements

University of Manchester Prof Anna Nicolaou Dr Amy Saunders Unilever SEAC Gary Sassano

This work was funded by Unilever as part of its

  • ngoing program developing novel approaches

for assuring consumer safety